Apoptosis-stimulating of p53 protein 2 (ASPP2) also known as Bcl2-binding protein (Bbp) and tumor suppressor p53-binding protein 2 (p53BP2) is a protein that in humans is encoded by the TP53BP2gene. Multiple transcript variants encoding different isoforms have been found for this gene.
ASPP2 (amino acid residues 600 –1128) was initially identified as 53BP2 (p53-binding protein 2) in a yeast two hybrid screen using p53 as the bait. Another yeast two hybrid screening in which Bcl-2 was used as the bait gave rise to the discovery of another fragment of ASPP2 (residues 123-1128) and it was called Bbp. The full length ASPP2 (1128 amino acids) was identified later.
ASPP2 contains several structural and functional domains. Its N-terminus (residues 1–83) has the structure of a β-grasp ubiquitin-like fold. It is followed by a predicted α-helical domain located between aa 123 and 323. and a proline-rich (ASPP2 Pro) domain between aa 674 and 902. The C-terminal part of ASPP2 contains four ankyrin repeats and an SH3 domain involved in protein-protein interactions. ASPP2 is found in the perinuclear region of the cytoplasm.
The ASPP family includes ASPP1, ASPP2, and iASPP. The name ASPP stands for apoptosis stimulating protein of p53, the name emphasizes the ankyrin repeats, SH3 domain, and proline-rich domains that characterize this family. The three family members come from different genes but ASPP1 and ASPP2 share a greater sequence similarity than either does with iASPP as the N terminus of iASPP has no homology with ASPP1 and ASPP2. The sequence similarities among ASPP family members indicates that ASPP1 and ASPP2 probably have similar biological functions that differ from that of iASPP. The family plays a key role in apoptosis regulation in the intrinsic and extrinsic apoptotic pathways. ASPP1 and ASPP2 promote, while iASPP inhibits, apoptosis.
ASPP2 is the ASPP family member with the most known binding partners. The highly conserved C-terminus was first known to bind to p53 through its ankyrin repeats and SH3 domain in 1994 by a yeast two hybrid system and it was called p53 Binding Protein 2 (53BP2). Other binding partners have been discovered through the years, indicating the importance of the ankyrin repeats and SH3 domains for protein-protein interactions. Some of the known binding partners of ASPP2 include BCL2, p63, p73, Hepatitis C virus core protein, Amyloid-b-Precursor Protein-Binding Protein 1 (APP-BP1), YES-Associated Protein (YAP), Adenomatosis Polyposis Coli 2 (APC2), RelA/p65, Protein Phosphatase 1 (PP1) and NFκB (p65)
The expression of ASPP2 is encoded by the gene TP53BP2 and is located in the long arm of chromosome 1 at q42.1. Northern-blot analyses showed that the ASPP2/53BP2 mRNA was expressed in many human tissues such as heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, but at varying levels. The highest expression level of ASPP2 was detected in skeletal tissue.
Levels of expression of ASPP2 are important, high levels of expression play an important role in inducing apoptosis independently of p53, mediated by p63 and p73. The expression is enhanced in response to DNA damage. On the other hand, silencing of ASPP2 expression by methylation was observed in several human carcinoma cells.
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